Analysis of FOXG1 Is Highly Recommended in Male and Female Patients with Rett Syndrome.

Department of Medical Genetics, University and University Hospital Antwerp, Antwerp.

Abstract

We screened a cohort of 5 male and 20 female patients with a Rett spectrum disorder for mutations in the coding region of FOXG1, previously shown to cause the congenital variant of Rett syndrome. Two de novo mutations were identified. The first was a novel missense mutation, p.Ala193Thr (c.577G>A), in a male patient with congenital Rett syndrome, and the second was the p.Glu154GlyfsX301 (c.460dupG) truncating mutation in a female with classical Rett syndrome, a mutation that was previously reported in an independent patient. The overall rate of FOXG1 mutations in our cohort is 8%. Our findings stress the importance of FOXG1 analysis in male patients with Rett syndrome and in female patients when mutations in the MECP2 and CDKL5 genes have been excluded.

Mutations in FOXG1 identified to date. The 2 mutations found in male patients are indicated at the top. Missense mutations are indicated in red, the mutations identified in this study are indicated in italics. FBD = Forkhead-binding domain; GBD = Groucho-binding domain; JBD = JARID1B-binding domain.